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A MULTICENTER STUDY ON THE EFFICACY, SAFETY AND PHARMACOKINETICS OF I10E IN PATIENTS WITH PRIMARY IMMUNODEFICIENCY (PID)

Phase 1
Conditions
a primary immunodeficiency as defined by the ESID and validated by a reference centre :• X-linked agammaglobulinemia (XLA)• Autosomal recessive inherited agammaglobulinemia (including autosomal recessive hyper-IgM syndrome)• Common variable immunodeficiency (CVID)• IgG subclass deficiency (at least 2 subclasses) with clinical manifestations of immunodeficiency
MedDRA version: 12.1Level: LLTClassification code 10010112Term: Common variable immunodeficiency
Registration Number
EUCTR2010-023483-41-FR
Lead Sponsor
FB BIOTECHNOLOGIES
Brief Summary

Not available

Detailed Description

Not available

Recruitment & Eligibility

Status
ot Recruiting
Sex
All
Target Recruitment
62
Inclusion Criteria

1. Both genders

2. Age between 2 to 70 year old

3. Has an humoral primary immunodeficiency as defined by the ESID and validated by the reference centers :
• X-linked agammaglobulinemia (XLA)
• Autosomal recessive inherited agammaglobulinemia (including autosomal recessive hyper-IgM syndrome)
• Common variable immunodeficiency (CVID)
• IgG subclass deficiency (at least 2 subclasses) with clinical manifestations of immunodeficiency

4. The requirement of IVIG therapy at a dose between 0.2 to 0.8 g/kg and at administration interval of 3-weeks or 4-weeks may be considered medically necessary for the treatment of the patient condition

5. Patient already under IgG replacement therapy with a stable dosage and with 3 documented trough levels >= 4 g/l within 6 months prior to the introduction of I10E or naïve. All these patients must be stabilized under I10E during the first 6 months during the study with IgG trough levels >= 6 g/L).

6. Written informed consent obtained prior to any study-related procedure and study product administration from either the patient or the patient's legal representative

7. If required by national regulation, registered with a social security or health insurance system
Are the trial subjects under 18? yes
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1. Patient already under IgG replacement therapy with no 3 documented trough levels >= 4 g/l within 6 months prior to the introduction of I10E

2. Known allergy or history of serious adverse reaction to any IgG

3. Patient with known antibodies to IgA

4. Chronic renal insufficiency or creatinin clearance values < 80 ml/min in adult patients (Modified Diet in Renal Disease) or < 60 ml/min in paediatric patients (Schwartz formula)

5. History of cardiac insufficiency (NYHA III/IV), cardiomyopathy, congestive heart failure, or severe hypertension

6. History of thrombotic episodes (including deep vein thrombosis, myocardial infarction, cerebrovascular accident, pulmonary embolism) within the last 12 months

7. Loop diuretic treatment within the last week before inclusion

8. Any additional cause of immunodeficiency, other than a primary immunodeficiency (as acquired immunodeficiency, lymphocytopenia, neutropenia, malignancy of lymphoïd cells, allogeneic hematopoïetic stem cell transplantation)

9. Need of routine premedication by steroid before IgG infusionsinfusions

10. Acute infection requiring antibiotics within one week before inclusion

11. Immunosuppressive agents, including anti-CD20 antibodies, within the last 6 months

12. Need of therapy with forbidden medication (steroid bolus, prophylactic antibiotic) that cannot be discontinued during the study

13. Protein-loosing enteropathy characterised by serum protein levels < 60 g/l and serum albumin levels < 30 g/l or nephrotic syndrome characterised by proteinuria >= 3.5 g/24 hours, serum protein levels < 60 g/l and serum albumin levels < 30 g/l

14. Any serious medical conditions that would interfere with the clinical assessment of I10E or prevent the patient to comply with the protocol requirements

15. Patient known to be infected with hepatitis B virus, hepatitis C virus, or human immunodeficiency virus.

16. Malignant disease other than a adequately treated basal cell or squamous cell skin carcinoma or in situ cervix carcinoma

17. Administration of another investigational product within the last month

18. Exposure to blood products or derivatives other than commercial IgG, within 3 months prior to inclusion.

19. Pregnant with positive results on a HCG-based pregnancy blood test (> 12 years) or breastfeeding woman, or woman of childbearing potential with no effective contraception (injectable, patch or combined oral estro-progestative or progestative contraceptives, intra-uterine devices of type 'copper T' and levonorgest releasing IU systems, depot intramuscular medroxyprogesteron, subcutaneous implants of progestative contraceptives implants).

20. Blood levels of total bilirubin > 2 x upper limit of normal range, alanine aminotransferase (ALT) or aspartate amino transferase (AST) > 3 x upper limit of normal range.

21. Anticipated poor compliance of patient with study procedures

Study & Design

Study Type
Interventional clinical trial of medicinal product
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Main Objective: To assess the efficacy of I10E in preventing acute serious bacterial infections;Secondary Objective: To assess the safety, efficacy, pharmacokinetic of I10E;Primary end point(s): The primary endpoint is the number of acute serious bacterial infections (aSBI) per patient and per year (annualized rate) as defined by the FDA guidance 70 FR 72124 and evaluated by the DSMB:<br>•bacteraemia or sepsis, <br>•bacterial meningitis, <br>•osteomyelitis / septic arthritis, <br>•bacterial pneumonia, <br>•visceral abscess.<br>
Secondary Outcome Measures
NameTimeMethod
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